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Transient Disruption of Adenosine Signaling During Embryogenesis Triggers a Pro-epileptic Phenotype in Adult Zebrafish

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Abstract

Adenosinergic signaling has important effects on brain function, anatomy, and physiology in both late and early stages of development. Exposure to caffeine, a non-specific blocker of adenosine receptor, has been indicated as a developmental risk factor. Disruption of adenosinergic signaling during early stages of development can change the normal neural network formation and possibly lead to an increase in susceptibility to seizures. In this work, morpholinos (MO) temporarily blocked the translation of adenosine receptor transcripts, adora1, adora2aa, and adora2ab, during the embryonic phase of zebrafish. It was observed that the block of adora2aa and adora2aa + adora2ab transcripts increased the mortality rate and caused high rate of malformations. To test the susceptibility of MO adora1, MO adora2aa, MO adora2ab, and MO adora2aa + adora2ab animals to seizure, pentylenetetrazole (10 mM) was used as a convulsant agent in larval and adult stages of zebrafish development. Although no MO promoted significant differences in latency time to reach the seizures stages in 7-day-old larvae, during the adult stage, all MO animals showed a decrease in the latency time to reach stages III, IV, and V of seizure. These results indicated that transient interventions in the adenosinergic signaling through high affinity adenosine receptors during embryonic development promote strong outcomes on survival and morphology. Additionally, long-term effects on neural development can lead to permanent impairment on neural signaling resulting in increased susceptibility to seizure.

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Acknowledgments

FPM is a fellowship recipient of Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). RSS is a Research Career Awardees of the CNPq/Brazil (Proc: 301599/2016-5).

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Authors and Affiliations

  1. Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Biologia Celular e Molecular, Escola de Ciências, PUCRS, Avenida Ipiranga, 6681, Porto Alegre, RS, 90619-900, Brazil

    Fabiano Peres Menezes, Felipe Machado Torresini & Rosane Souza da Silva

  2. Laboratório de Biologia do Desenvolvimento do Sistema Nervoso, Departamento de Biologia Celular e Molecular, Escola de Biociências, PUCRS, Porto Alegre, RS, Brazil

    Laura Roesler Nery

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  1. Fabiano Peres Menezes
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  2. Felipe Machado Torresini
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  4. Rosane Souza da Silva
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Correspondence to Rosane Souza da Silva.

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All protocols followed National Institutes of Health guide for the care and use of Laboratory animals (NIH Publications No. 8023, revised 1978) and the Brazilian legislation and were approved by the Institutional Animal Care Committee of PUCRS registered under the protocol number 14/00416—CEUA/PUCRS.

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Menezes, F.P., Machado Torresini, F., Nery, L.R. et al. Transient Disruption of Adenosine Signaling During Embryogenesis Triggers a Pro-epileptic Phenotype in Adult Zebrafish. Mol Neurobiol 55, 6547–6557 (2018). https://doi.org/10.1007/s12035-017-0850-6

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